Leukocyte Markers and cytokines

· T cells:

· CD3 and the zeta chains are part of the T-cell receptor (TCR) complex that send signals intracellularly when the TCR binds with the appropriate antigen on an MHC molecule.

· CD28 is a part of the TCR complex that sends activating signals intracellularly when bound to coreceptors on the APC such as CD80 or CD86 (B7-1 and B7-2?).

· CTLA-4 receptors can also receive B7-1 and B7-2 molecules from APCs, but they send an inhibitory signal intracellularly, resulting in anergy.

· CD4 attaches to the non-antigen part of class II MHC molecules and sends intracellular signals when the TCR matches the antigen.

· CD8 attaches to the non-antigen part of class I MHC molecules and sends intracellular signals when the TCR matches the antigen.

1. CD8-positive T cells express cytotoxic proteins: perforin, granzyme B, T cell intracellular antigen (TIA)-1

· CD25 is the alpha-chain of the IL-2 receptor, which is constitutively expressed by some regulatory T cells.

· FasL is a membrane-bound TNF molecule, expressed by activated T cells, which induces apoptosis in the receiving cell when bound to Fas.

· B cells:

· IgM and IgD are present on the surface of all naive B cells, and they form the antigen-specific part of the B cell receptor complex.

· CD20 is part of the B cell receptor complex found in mature B cells. It binds to complement extracellularly, and sends a signal intracellularly. This is also the receptor used by the Epstein-Barr virus (EBV) to infect B cells.

· CD40 is a member of the tumour necrosis factor (TNF) receptor family, and it receives CD40 ligand, found on activated helper T cells. This interaction is essential for B cell maturation and secretion of IgG, IgA, and IgE antibodies. CD40 is also expressed on macrophages, allowing activated helper T cells to activate macrophages as well.

· CD19 is a B-lineage marker found on pre-B cells (and mature B cells?)

· CD79a is a broad-spectrum B cell marker (immature and mature B cells)

· CD138 is a plasma cell marker

· Dendritic cells:

· TLRs (toll-like receptors) recognize a variety of alien microbial markers, and activate a general innate immune response.

· MHC-II (major histocompatibility class II) molecules present processed antigen to CD4+ T cells. MHC-II is generally only expressed by antigen-presenting cells such as macrophages, dendritic cells, and B cells.

· B7-1 and B7-2 are costimulatory molecules that are required to activate CD4+ T cells when binding to the MHC-II complexes.

· NK (Natural Killer) cells:

· CD16 or Fc receptor binds to the nonspecific ends of IgG and allows the NK cell to lyse IgG-coated cells.

1. Relatively specific for NK cells

· CD56.

· They can express T cell markers such as CD2, CD7, CD8, CD56, and CD57

· CD3 (polyclonal antibodies, cytoplasmic),

· Cytotoxic proteins: perforin, granzyme B, T cell intracellular antigen (TIA)-1

· Mast cells:

· CD117

· MHC-I (major histocompatibility class I) molecules present intracellular antigens, and are expressed by all nucleated human cells and platelets.

· Fas (CD95) is a member of the TNF-receptor family, expressed on many types of cells. When activated by FasL, it induces apoptosis in the cell.

· TdT is a marker for immature/blastic tumours.

· Cytokines:

· Those that mediate innate immunity: IL-1, TNF (see also later), type 1 interferons, and IL-6.

· Those that are involved in both innate and adaptive immunity: IL-12 and IFN-gamma (see also later).

· IL-2 is an important growth factor for T cells. The IL-2 receptor is a target for anti-rejection drugs.

· IL-4 stimulates T cells to differentiate along the TH2 pathway. It also acts on B cells.

· IL-6 is a growth factor for B cells.

· IL-15 stimulates growth and activity of NK cells.

· IL-10 and TGF-ß downregulate immune responses.

· IFN-gamma is the key mediator of delayed-type hypersensitivity (TH1). It also activates macrophages (among other things).

· IL-5 activates eosinophils.

· TNF and lymphotoxin (TNF-ß) activate neutrophils and endothelial cells into the inflammatory process. TNF also produces the systemic acute phase response along with IL-1.

· Chemokines recruit individual types of leukocytes to sites of inflammation.

· CSFs (colony-stimulating factors) stimulate the production and growth of new blood cells.

· Stem cell factor (c-kit ligand) stimulates the proliferation of pluripotent stem cells.

· IL-13 promotes IgE production and stimulates mucous secretion.

· IL-12 is produced by macrophages and dendritic cells, and is critical for the development of the TH1 response.

· IL-7 is required for the proliferation of lymphoid progenitors, particularly T cell precursors.